A Popular Science Article on the State of Epigenetic Clocks

This popular science article is a good view of the present state of development and use of epigenetic clocks, covering the issues as well as the promise. Epigenetic age can be measured, with many different clocks using many different combinations of DNA methylation sites on the genome, and greater epigenetic age correlates with greater mortality and risk of age-related disease. What processes of aging actually drive epigenetic age, however? How will epigenetic age change following interventions that target only one or only several of the myriad causes and consequences of aging? Will those changes accurately reflect outcomes on mortality and disease risk? No-one knows, which is why it is currently difficult to use epigenetic clocks to assess the ability of any given approach to produce rejuvenation or a slowing of aging.

Despite their obvious promise and growing popularity, epigenetic clocks still have some notable shortcomings. First, it's difficult to tell exactly how accurate biological age measurements are. Epigenetic clocks are much better at predicting lifespan than previous techniques, like oxidative damage or telomere length. But the challenge with longevity research is that studies to determine whether biological age predictions translate to actual lifespans take decades. In other words, if you're 25 with a biological age of 30, will you die five years sooner than average? Secondly, scientists haven't pinpointed which changes are directly caused by aging. It's possible that some changes occur by happenstance in older people, independent of aging. In other words, some changes we associate with aging may not actually impact the length or quality of our lives.

Finally, some scientists suspect that epigenetic clocks are more of a measure of biological age than a driver of it. "Think of the clock as a wristwatch. If you broke your wristwatch, the time would still go on. My guess would be that if we stopped these methylation sites from changing, we wouldn't interfere much with the aging process." But these researchers still see epigenetic clocks as an excellent marker for biological age, a measure of how quickly the aging process is proceeding in humans or other animals, independent of calendar years. For example, a smoker at age 50 might have an epigenetic age of 65, while a person at the same who exercises frequently might have an epigenetic age of 45. Others are a bit more optimistic. "I would say there are DNA methylation sites that actually matter a lot. If you change the right locations, you may actually rejuvenate cells. I won't claim that, I'm just saying nobody knows."

Epigenetic clocks remain a powerful tool in the science of rejuvenation. In the short term, researchers believe their best use is as a measuring tool, a kind of epigenetic yardstick that determines whether other interventions are successful. Although there are outstanding questions about how we define aging, how we measure rejuvenation, and how this could unfold economically, epigenetic clocks are "a true revolution." When it comes to aging research in humans, epigenetic clocks could be a tool that helps quantify a treatment's effectiveness while subjects are still alive. In other words, if epigenetic clocks become sophisticated enough that the FDA accepts them as surrogate endpoints, it would allow researchers to quickly demonstrate a drug's efficacy in mere months by measuring methylation - as opposed to waiting years to see how the drug affects survival. Longevity research could speed ahead, no longer reliant on death as a primary endpoint.

Link: https://neo.life/2022/09/2-minutes-to-midlife-the-fantastic-unspecified-future-of-epigenetic-clocks/

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